PowerLecture: Chapter 15

1
PowerLectureChapter 15

• Controls over Genes

2
Impacts, Issues Between You and Eternity

• Loss of gene controls can be disastrous
• Some gene mutations, either inherited or
  spontaneously mutated due to environmental
  factors, predispose individuals to develop
  cancer
• ERBB2, a type of membrane receptor, is encoded on
  chromosome 17
• This gene controls the cell cycle -
  overexpression or mutation triggers cancerous
  transformations

3
Impacts, Issues Between You and Eternity

• BRCA1 and BRCA2 are tumor suppressing proteins
  that fix damaged DNA
• Breast cancer cells often contain their mutated
  forms

4
Changes in DNA Trigger Cancer

• Ultraviolet radiation can cause breaks
• Can promote formation of dimers

5
Controlling the Cell Cycle

• Cycle has built-in checkpoints
• Proteins monitor chromosome structure, whether
  conditions favor division, etc.
• Proteins are products of checkpoint genes
• Kinases
• Growth factors

6
Oncogenes

• Have potential to induce cancer
• Mutated forms of normal genes
• Can form following insertions of viral DNA into
  DNA or after carcinogens change the DNA

7
Cancer Characteristics

• Plasma membrane and cytoplasm altered
• Cells grow and divide abnormally
• Weakened capacity for adhesion
• Lethal unless eradicated

8
Apoptosis

• Programmed cell death
• Signals unleash molecular weapons of
  self-destruction
• Cancer cells do not commit suicide on cue

9
Gene Control

• Which genes are expressed in a cell depends
  upon
• Type of cell
• Internal chemical conditions
• External signals
• Built-in control systems

10
Mechanisms of Gene Control

• Controls related to transcription
• Transcript-processing controls
• Controls over translation
• Post-translation controls

11
Regulatory Proteins

• Can exert control over gene expression through
  interactions with
• DNA
• RNA
• New polypeptide chains
• Final proteins

12
Control Mechanisms

• Negative control
• Regulatory proteins slow down or curtail gene
  activity
• Positive control
• Regulatory proteins promote or enhance gene
  activities

13
Control Mechanisms

• Promoters
• Enhancers

14
Chemical Modifications

• Methylation of DNA can inactivate genes
• Acetylation of histones allows DNA unpacking and
  transcription

15
Controls in Eukaryotic Cells

• Control of transcription
• Transcript processing controls
• Controls over translation
• Controls following translation

16
Controls in Eukaryotic Cells
NUCLEUS
CTYOPLASM
translational control
pre-mRNA transcript
protein product
mRNA
mRNA
DNA
protein product control
mRNA degradation control
mRNA transport control
transport processing control
transcription control
inactivated protein
inactivated mRNA
Fig. 15-3, p.233
17
Chromosome Puff

• Portion of the chromosome in which the DNA has
  loosened up to allow transcription
• Translation of transcripts from puffed region
  produces protein components of saliva

18
X Chromosome Inactivation

• One X inactivated in each cell of female
• Creates a mosaic for X chromosomes
• Governed by XIST gene

19
X Chromosome Inactivation

• A condensed X chromosome (Barr body) in the
  somatic cell nucleus of a human female

Fig. 15-4a, p.234
20
Most Genes Are Turned Off

• Cells of a multicelled organism rarely use more
  than 5-10 percent of their genes at any given
  time
• The remaining genes are selectively expressed

21
Phytochrome

• Signaling molecule in plants
• Activated by red wavelengths, inactivated by
  far-red wavelengths
• Changes in phytochrome activity influence
  transcription of certain genes

22
petal
carpel
stamen
sepal
Fig. 15-6, p.235
23
B
A
C
1
2
3
4
petals
carpel
sepals
stamens
Fig. 15-6, p.235
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Fig. 15-6, p.235
25
Fig. 15-6, p.235
26
Fig. 15-6, p.235
27
Fig. 15-6, p.235
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Fig. 15-6, p.235
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Homeotic Genes

• Occur in all eukaryotes
• Master genes that control development of body
  parts
• Encode homeodomains (regulatory proteins)?
• Homeobox sequence can bind to promoters and
  enhancers

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Knockout Experiments

• Prevent a genes transcription or translation
• Differences between genetically engineered
  knockout individuals and wild-type individuals
  point to function of knocked out gene
• Knockout experiments shed light on genes that
  function in Drosophila development

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Knockout Experiments
Fig. 15-7c, p.237
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Body Plan
A7
A5
A3
A1
T2
T2
T2
A8
A4
A2
T3
T1
T2
A8
A7
A6
A5
A4
A3
A2
A1
Md
T3
Mx
T1
T2
Lb
A8
A7
A6
T1
T2
A4
A3
A1
T3
A2
A5
A4
A3
A2
T1
T3
A1
T2
A6
A7
A8
Fig. 15-8a, p.237
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Body Plan
Fig. 15-8b, p.237
34
Body Plan
Fig. 15-8c, p.237
35
Gene Control in Prokaryotes

• No nucleus separates DNA from ribosomes in
  cytoplasm
• When nutrient supply is high, transcription is
  fast
• Translation occurs even before mRNA transcripts
  are finished

36
The Lactose Operon
operator
regulatory gene
gene 1
gene 2
gene 3
operator
transcription, translation
promoter
lactose operon
repressor protein
Fig.15-10, p. 241
37
High Lactose
allolactose
lactose
mRNA
RNA polymerase
gene 1
operator
operator
promoter
Fig.15-10, p. 241
38
Low Lactose

• Repressor binds to operator
• Binding blocks promoter
• Transcription is blocked

Fig.15-10, p. 241
39
CAP Exerts Positive Control

• CAP is an activator protein
• Adheres to promoter only when in complex with
  cAMP
• Level of cAMP depends on level of glucose

40
Positive Control High Glucose

• There is little cAMP
• CAP cannot be activated
• The promoter is not good at binding RNA
  polymerase
• The lactose-metabolizing genes are not
  transcribed very much

41
Positive Control Low Glucose

• cAMP accumulates
• CAP-cAMP complex forms
• Complex binds to promoter
• RNA polymerase can now bind
• The lactose-metabolizing genes are transcribed
  rapidly

42
Hormones

• Signaling molecules
• Stimulate or inhibit activity in target cells
• Mechanism of action varies
• May bind to cell surface
• May enter cell and bind to regulatory proteins
• May bind with enhancers in DNA

43
Polytene Chromosomes

• Occur in salivary glands of midge larvae
• Consist of multiple DNA molecules
• Can produce multiple copies of transcripts

44
Vertebrate Hormones

• Some have widespread effects
• Somatotropin (growth hormone)?
• Others signal only certain cells at certain times
• Prolactin stimulates milk production

45
Fig. 15-11a, p.241
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Fig. 15-11b, p.241